SU116 - ASSOCIATION BETWEEN THE NEURONAL CELL ADHESION MOLECULE (NrCAM) GENE VARIANTS, WORKING MEMORY AND COGNITION IN METHAMPHETAMINE ABUSE

Abstract

Background The recent development of molecular genetic techniques is promoting the study of the genetic basis of drug abuse. It is possible that personality factor mediates intermediately in the genetic contributions to drug abuse. Classical genetic studies document strong complex genetic contributions to abuse of multiple addictive substances, to mnemonic processes that are likely to include those involved in substance dependence, and to the volumes of brain gray matter in regions that are likely to contribute to mnemonic/cognitive and to addictive processes. [1] Several lines of evidence support a role of the neuronal cell adhesion molecule (NrCAM) in polysubstance abuse vulnerability in humans, as well as in the rewarding effects of abused drugs in animals. [2] This gene, which encodes a receptor involved in nervous system development, is expressed in the central nervous system and located in the 7q region. Polymorphisms in NrCAM have been reported to be associated with addiction susceptibility and with substance abuse, implicating NrCAM in reward circuitry. Methods Thirty-seven male methamphetamine abusers(age=43.3±7.8) and thirty unrelated controls (16 males, 14 females; age=59.8±10.4) were enrolled into the study from the Bugok National Hospital drug abuse clinic for one year. They underwent a blood sample collection for NRCAM gene variants genotyping. Wizard Genomic DNA Purification Kit was used for extracting DNA from patient's blood collected in EDTA tubes. 10 single nucleotide polymorphisms(SNPs) in NrCAM gene were selected for variant analysis. We evaluated working memory dimensions with Hinting Task(HT), Eye Task (ET), Picture Sequencing (PS), Emotion Attribution Task (EAT), Emotion Recognition 40 (ER40), Wisconsin Card Sorting Test (WCST). We assessed cognitive dimensions with Iowa Gambling Task (IGT) and Game of Dice Tast (GDT). Results The distribution of one NRCAM gene SNP genotypes and alleles significantly differed between patients and controls.(rs1990162; p=0.0418) Five NRCAM gene SNP genotypes and alleles were associated with some working memory dimensions in the patients.(rs2142325, rs381318, rs1269621, rs2072546, rs1269634) Of those SNP rs1269634 was associated with three working memory dimensions comprehensively.(PS-M, EAT, WCST-PE) Two NRCAM gene SNP genotypes and alleles were associated with some cognitive dimensions in the patients.(rs2142325, rs722519) Both SNPs were associated with four cognitive dimensions comprehensively.(IGT-A, B, C, D, B3, B5) Only one SNPs(rs2142325) was associated with both working memory and cognitive dimensions. Discussion These findings support the idea that NRCAM gene polymorphisms could play a part in the genetic susceptibility to methamphetamine abuse, and it seems to be involved in predisposing addictive patients to a more disturbed addictive behavior influencing on each working memory and cognitive factor. Considering the important role of the NRCAM gene in brain development, our results therefore replicate that the NRCAM gene is one of the strong candidate genes for drug abuse.